INTERACTION OF HEMOGLOBIN/EDRF IN CARDIOVASCULAR CONTROL

如果心血管疾病，血红蛋白将被用作血液替代品 这些溶液的作用不会造成明显的毒性。这个 这项应用的目的是确定 狗的牛聚合血红蛋白。由于血红蛋白与硝酸根结合 氧化物我们建议的具体目标是确定血红蛋白如何 干扰了NO对循环的生理控制。最多的 给药后血液循环发生明显变化 含有血红蛋白的溶液会增加动脉血压和 血管阻力。对责任机制的理解 这是由反射引起的部位阻力的增加和调制 机制将是这项提议的第一个具体目标。第二 具体目标将集中在含血红蛋白溶液的能力上 去寻觅不。这主要取决于四聚体的能力 血红蛋白在内皮细胞和底层细胞之间扩散 平滑肌细胞。我们认为，血红蛋白的聚合物不会 由于体积较大而弥漫，不会增加动脉压。 毕竟，红血球中含有的血红蛋白不会清除。 间隙EDRF。我们建议的第三个具体目标是 含有血红蛋白的溶液也会改变氧气的利用方式。 通过周围组织。这是基于观察到的 取代精氨酸分子对NO生成的显著抑制 改变心脏和骨骼肌的氧气提取和消耗。 第四个具体目标是确定重复服用 含血红蛋白溶液改变血液中一氧化氮的产生 血管以及与此相关的生化和分子机制。 我们的研究将在慢性器械犬和组织中进行。 来自相同的动物。这一点，我们相信将允许推断我们的 对男性心血管控制的结果和对 血红蛋白修饰的心血管调控机制 包含解决方案。

Hemoglobins will be used as a blood substitute if the cardiovascular actions of these solutions do not cause significant toxicity. The objective of this application is to determine the physiologic actions of bovine polymerized hemoglobins in dogs. Since hemoglobin binds nitric oxide the specific aims of our proposal are to determine how hemoglobin interferes with the physiologic control of the circulation by NO. The most obvious change which occurs in the circulation after administration of hemoglobin containing solutions is an increase in arterial pressure and vascular resistance. An understanding of the mechanisms responsible for this, the site of the increase in resistance and modulation by reflex mechanisms will be the first specific aim of this proposal. The second specific aim will focus on the ability of hemoglobin containing solutions to scavenge NO. This depends primarily on the ability of tetrameric hemoglobin to diffuse between the endothelial cell and the underlying smooth muscle cell. We propose that polymers of hemoglobin will not diffuse due to the large size and will not increase arterial pressure. After all, hemoglobin contained in red cells does not scavenge interstitial EDRF. The third specific aim of our proposal is that hemoglobin containing solutions also alter the way in which oxygen is used by the peripheral tissues. This is based on the observation that inhibition of NO formation using substituted arginine molecules markedly alters oxygen extraction and consumption by the heart and skeletal muscle. The fourth specific aim is to determine if the repeated administration of hemoglobin containing solutions alters the production of NO by blood vessels and the biochemical and molecular mechanism responsible for this. Our studies will be conducted in chronically instrumented dogs and tissues from the same animals. This, we believe will allow extrapolation of our results to cardiovascular control in man and to a understanding of the mechanisms of cardiovascular control which are modified by hemoglobin containing solutions.